The analysis of gene expression has revolutionized our understanding of fundamental questions in biology and the study of clinical disorders. The two traditional approaches to study gene expression are microarray analysis for high-throughput studies under a limited set of conditions and real-time polymerase chain reaction (PCR) for precise and sensitive quantification of a few genes. The relative lack of sensitivity and high expense in microarray analysis are major bottlenecks limiting the discovery of gene expression changes during biological processes and hindering systems-biological approaches to gene regulation. The high reagent costs and laborious sample handing associated with traditional real-time PCR analysis have generally precluded high-throughput analysis using this otherwise powerful approach. The development of microfluidic technologies to precisely manipulate nanoliter liquid volumes has dramatically increased the potential throughput of real-time PCR studies. The state-of-the-art BioMark High-Throughput Genetic Analysis System uses integrated fluidics circuits (IFCs) to combine the precision and sensitivity of real-time PCR with extremely high-throughput at a fraction of the costs. Further, this system is capable of single nucleotide polymorphism (SNP) genotyping at a throughput amenable to large-scale population genetics studies, high-throughput copy number variation analysis, and digital PCR applications that provide highly quantitative analysis of gene expression from single cells. A consortium of 13 NIH-funded researchers at the University of Pennsylvania School of Medicine, School of Arts and Sciences and Temple University, whose research is supported by 68 NIH grants, will be major users of the requested BioMark system, which will be housed in the University of Pennsylvania Microarray Core Facility. The projects supported by this equipment application will take advantage of the capabilities of the BioMark System to study critical behavioral and biomedical questions that cannot be addressed with the currently available microarray and low throughput real- time PCR systems at the University of Pennsylvania. These studies promise to revolutionize our understanding of the biological processes underlying circadian rhythms, memory storage, sleep, psychiatric disease, metabolic regulation and cardiovascular function, laying the groundwork for the future development of novel therapeutic approaches to a variety of disorders.